Plant antitumor agents and their analogs have continuously been an excellent source of new drugs for cancer chemotherapy, as well as novel biochemical probes for the elucidation of tumor cell biology. The longterm objective of this research is to discover novel cytotoxic antisolid tumor compounds from plant-derived natural products and their analogs. Specifically, we propose continuously to isolate and characterize the potent cytotoxic principles from extracts of 66 previously unexplored species of U.S., Taiwan, and China origin in 40 families. These extracts have already demonstrated potent cytotoxicity in an in-house panel of in vitro human tumor cell lines (HTCL), including A-549 (lung carcinoma), HCT-8 (colon carcinoma), MCF-7 (breast adenocarcinoma) , RPMI-7951 (melanoma), and TE-671 (medulloblastoma). Extraction, fractionation, and isolation of the active principles will be guided at every stage by an in vitro cytotoxicity assay in either A-549, HCT-8, o- T-MCF-7, RPMI-7951, TE-671, depending upon the initial selective cytotoxicity demonstrated by the crude extracts. Following the above bioassay-directed isolation of the active principles, the determination of their structures will be carried out by modern physical methods, including spectral and X-ray analyses. Structural modification and synthesis of analogs of selected new active leads in order to elucidate their structure-activity relationships and mechanism of action, as well as to improve their pharmacological profiles will also be initiated. The new water-soluble 2-phenyl-4-quinolones will be synthesized and evaluated as potential anti-solid tumor drugs. All active compounds will be submitted to the National Cancer Institute, NIH, for further in vitro HTCL panels and in vivo xenograft tumor models evaluations.